ABSTRACT Tissue ablation during thermal therapies, such as focused ultrasound (FUS), result in tissue necrosis and irreversible changes in cell- and macromolecular-structure. The success of thermal therapies is defined in terms of adequately treating the desired target while sparing surrounding normal tissues. This demands methods for accurately determining tissue viability in real time so that treatments be efficacious, efficient and safe. Imaging methods that can detect irreversible tissue changes correlated to long-term effects are crucial for endpoint assessment and the general success and wide adoption of thermal therapies. The MR temperature imaging methods currently used are not always accurate, and the addition of other independent measurements of tissue viability are needed . In this application, we propose to develop and test a novel MRI pulse sequence to simultaneously measure four MR-derived parameters sensitive to tissue damage. Our sequence will first measure maps of the proton resonance frequency shift, from which temperature change and cumulative thermal dose can be calculated. Simultaneously, it measures the T1- relaxation time, which indicates temperature change in fat and evidence of fluid change at the point of ablation, as well as shear wave velocity, a direct measure of tissue stiffness, which often changes with ablation. T1 relaxation is measured using a novel mono flip angle approach we recently developed. The PRF shift and shear wave velocity are encoded in the MR phase images, and can be separated using novel methods we have developed. Because of the simultaneous acquisition, these properties are automatically co-registered providing substantially more information about the evolving FUS-induced tissue changes than what is currently available. The addition of T1-mapping and shear modulus measurements will enable evaluations in adipose tissues, where the PRF method does not work, allowing for more complete evaluations in areas such as the breast and abdomen. The proposed project will immediately benefit our current complementary work in performing first-in-human breast MR-guided FUS treatments with our novel hardware that enables high signal-to-noise ratio image acquisition. This work is an important step towards our long-term goal of developing comprehensive real time measurements that can accurately monitor and predict tissue viability during and following MRgFUS.